The Role Of Osteocytes In Particle Induced Osteolysis
Funder
National Health and Medical Research Council
Funding Amount
$457,196.00
Summary
Hip replacements often fail due to the loss of adjacent bone. Metal or polyethylene particles are produced as the prosthesis bearing surface wears but how do these particles lead to bone loss? Our work suggests involvement of osteocytes within the bone mineral, which are increasingly understood to drive bone physiology and pathology. We will explore the role of the osteocytes by examining their response to particles, which may identify a new target to prevent particle-induced bone loss.
Targeting Bone Marrow Lesions To Find Interventions In The Progression Of Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$467,395.00
Summary
It is essential to elucidate the underlying cause(s) of osteoarthritis because our current level of understanding of this condition has failed to produce effective treatments. Lesions in the bone under the cartilage (BMLs), seen using MRI, have strong potential value for the objective monitoring and management of OA. However, because the nature of BMLs is not well understood, the aim of this application is to perform a comprehensive study of BMLs in OA bone.
Substance abuse is a significant social and economic burden upon Australian societies and on societies around the world. Treatment remains problematic due to the multi-layer nature of the disease, difficulties with treatment compliance and less than ideal treatment regimes. The present study aims to improve treatments for alcohol and drug abuse using pre-clinical models to identify and characterize a new brain system implicated in drug-seeking.
High Penetrance Deleterious Mutations In Blinding Glaucoma
Funder
National Health and Medical Research Council
Funding Amount
$1,345,055.00
Summary
This project aims to identify the genes most commonly mutated in individuals with advanced glaucoma. Identification of such genes will lead to improved understanding of glaucoma pathogenesis, a better ability to predict risk, and the identification of drug targets for novel therapies.
Salt (sodium) is an essential electrolyte. Our convincing and complementary findings provide compelling evidence for a link between evolutionarily ancient “instincts” and substance abuse. This proposal is translational, including studies in opiate dependent humans. Our studies will establish how and where in the brain endogenous opioids are implicated in the gratification of salt appetite, how salt appetite is altered in opiate dependency and if salt appetite recovers following opiate withdrawal
Determination Of Irradiation Dose Efficacy For Use In Impaction Grafting At Revision Joint Replacement
Funder
National Health and Medical Research Council
Funding Amount
$411,517.00
Summary
Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence ....Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence of early complications of this procedure have included loss of fixation within the bone. Fracture of the bone around prostheses has also reported in some centres. These events require more surgery, putting the patient at higher risk greater complications and longer rehabilitations. Recent improvements in surgical technique and donor bone preparation have improved results. A current debate questions whether the dose of irradiation can be reduced from 25 kGy, while maintaining sterility of allografts. The risk of bacterial contamination in allografts is low, and irradiation reduces the mechanical strength of the graft, contributing to complications when irradiated bone is used. The benefits of decontaminating the bone may be outweighed by the higher risk for failure due to poor bone quality and resulting prosthesis instability. We will use ISO standards to test the validity of radiation dose for sterilising bone ex vivo. In the absence of controlled human studies, our aim is also to compare the results of impaction grafting with non-irradiated bone versus bone irradiated at current doses used by Australian bone banks, and lower doses indicated by ex vivo testing. We will use a large animal model of revision hip replacement, with precise measures of prosthesis stability. The results of this study will guide clinical decisions regarding the efficacy of current bone graft preparation procedures and the use of irradiated bone in human hip replacement surgery.Read moreRead less
Role Of IGF Binding Protein-3 (IGFBP-3) And IGFBP-5 As Modulators Of Nuclear Hormone Signalling
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain ....The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain cells perform specialised functions. In test-tube experiments, IGFBP-3 and IGFBP-5 interact directly with the receptors that regulate the effects of these hormones. If the same thing happens inside the cell, IGFBP-3 and IGFBP-5 could change the way these receptors respond to signals from outside the cell. We will investigate what effect these IGFBPs have in living cells and in whole animals and how this may relate to human disease. If we are able to understand how IGFBP-3 and IGFBP-5 affect the way cells respond to vitamin A and D, then we may be able to develop new ways to treat certain human diseases.Read moreRead less
The Clinical Value Of Serology And Molecular Tests For Diagnosing Invasive Aspergillosis In At-risk Hematology Patients
Funder
National Health and Medical Research Council
Funding Amount
$1,095,500.00
Summary
Aspergillus is a fungus found in soil, on farms and on construction sites. In those whose immune system is impaired it causes severe infection. The people who are particularly at high-risk of Aspergillus infection (called Invasive Aspergillosis) are those with acute leukaemia on chemotherapy or post bone marrow transplantation. Currently 15% of those at high-risk get Invasive Aspergillosis and 58-93% of those infected die. The main reason for this high death rate is that our current diagnostic t ....Aspergillus is a fungus found in soil, on farms and on construction sites. In those whose immune system is impaired it causes severe infection. The people who are particularly at high-risk of Aspergillus infection (called Invasive Aspergillosis) are those with acute leukaemia on chemotherapy or post bone marrow transplantation. Currently 15% of those at high-risk get Invasive Aspergillosis and 58-93% of those infected die. The main reason for this high death rate is that our current diagnostic tests are not good at detecting infection or often only detect the infection at advanced stages when treatment is ineffective. Because of the limitations of current diagnostic tests the current practice is to give empiric antifungal therapy (EAFT) early to treat Invasive Aspergillosis. However studies have demonstrated that this therapy has only resulted in a minor reduction in the mortality rates and it causes significant drug toxicity. It is a suboptimal treatment modality. New tests have been developed to diagnose Invasive Aspergillosis. These tests are for the detection of an Aspergillus protein in blood and for the detection of Aspergillus DNA in the blood. Available data suggests that these new tests are sensitive in the detection of Invasive Aspergillosis. Also other studies suggest that these new tests make an early diagnosis and seem to be able to monitor responses to treatment. However no study has been performed to date which demonstrates that the use of these tests can impact on important patient outcomes. This trial is designed to determine whether the use of the new tests to guide therapy will help improve treatment of Invasive Aspergillosis, reduce drug toxicity and reduce the death rate in the high-risk patients as compared with the current standard method of diagnosis and treatment with EAFT. If the trial is successful then this represents a significant advancement in the treatment and survival of leukaemic and bone marrow transplantation patients.Read moreRead less
Whole Body Vibration For Osteoporosis: Shaking Up Our Treatment Options
Funder
National Health and Medical Research Council
Funding Amount
$961,017.00
Summary
Our aim is to examine the ability of vibration alone and in combination with osteoporosis drugs to reduce hip fracture in postmenopausal women. In Australia, 1 in 2 women >60yrs, will sustain an osteoporotic fracture. Only drugs notably decrease fracture; however none are entirely effective and some patients don’t respond. Whole body vibration has emerged as a potentially effective therapy. A combination of vibration and drugs may enhance the effects of both and revolutionise treatment.